THE FORMATION AND MEASUREMENT OF DNA NEUROADDUCTION IN ALCOHOLISM - CASE-REPORT

We present a case report of an intoxicated alcoholic driver who sustai ned fatal motor vehicle injuries. We subsequently quantified ethanol-d erived acetaldehyde (ACE) DNA products in his brain, which may represe nt a major contributor to clinical alcoholic use and complications. Fu rther, ACE DNA neuroadducts may indicate chronic exposure to alcohol, as demonstrated by P-32-prelabeled DNA and two-dimensional thin-layer chromatography. ACE and other unknown neuroadducts were evident in the histologically normal frontal, parietal, and caudate lobes. DNA neuro adduct formation was extensive and similar in three separate brain reg ions with normal histology. Contributing neuroadduction by chronic dru g abuse is also possible, though the deceased's terminal acute blood s creens for recent drug abuse were negative. The mechanism of alcohol n eurotoxicity remains unknown, but biochemical nonenzymatic changes of DNA at the nucleic acid level (adduct formation) can alter gene functi on and stability. DNA neuroadduct detection may represent an important determinant in quantifying neurotoxicity from drug abuse or alcoholis m in the absence of history, the presence of negative blood, tissue, a nd urine assays for recent drug and alcohol use, and the absence of ne uropathology.